Parasitology: Key Concepts, Hosts, Transmission, and Diagnosis

What is the primary role of p53?

p53 is the 'Guardian of the Genome'. It detects DNA damage and decides whether the cell should arrest, repair, or undergo apoptosis.

How does p53 detect DNA damage?

DNA damage activates ATM/ATR and Chk1/Chk2 kinases, which phosphorylate p53, preventing MDM2 binding and stabilizing active p53.

How does p53 control cell fate?

Activated p53 induces p21 for cell cycle arrest, DNA repair genes, and Bax/PUMA for apoptosis if damage is irreparable.

How is p53 usually regulated in healthy cells?

p53 induces MDM2, which binds p53, ubiquitinates it, and targets it for proteasomal degradation, creating a negative feedback loop.

How can the p53 pathway be lost in cancer?

Loss can occur due to TP53 mutation/deletion, MDM2 over-expression, ATM/Chk defects, or HPV E6-mediated degradation of p53.

What is the role of pRb?

pRb controls passage through the Restriction Point (R-point) at the G1 to S transition of the cell cycle.

How does pRb control the R-point?

Hypophosphorylated pRb binds E2F, blocking S-phase genes; phosphorylated pRb releases E2F, allowing DNA replication to begin.

How is pRb inactivated in cancer?

Inactivation can occur due to RB1 mutation/deletion, Cyclin D/CDK4 over-activity, or HPV E7 binding and inactivation of pRb.

Why are some tumour suppressor mutations dominantly acting?

Proteins like p53 function as tetramers, so a single mutant subunit can inactivate the whole complex, leading to a dominant-negative effect.

Why does HPV target both p53 and pRb?

HPV inactivation of p53 and pRb removes cell-cycle control and induces apoptosis, preventing division of damaged cells.

What do the HPV oncoproteins do?

E6 degrades p53, E7 inactivates pRb, and E5 increases growth signaling via EGFR, leading to persistent E6/E7 expression.

What is an oncogene?

An oncogene is a gain-of-function version of a proto-oncogene that drives constitutive proliferative signaling.

What are the main mechanisms of oncogene activation?

Activation can occur via point mutation (e.g., Ras), gene amplification (e.g., HER2), translocation with active promoter (e.g., MYC-IgH), or fusion genes (e.g., BCR-ABL).

Why is BCR-ABL constitutively active?

The fusion protein lacks standard regulatory control, leaving the Abl tyrosine kinase permanently activated, driving the progression of CML.

How does HPV E5 promote oncogenesis?

HPV E5 prevents EGFR degradation, causing its recycling and accumulation at the cell surface, leading to persistent growth signaling.

Compare HPV-driven cancer with sporadic colon cancer.

HPV cancer involves viral proteins inactivating p53/pRb (E6/E7), while colon cancer involves mutations in APC (Wnt), KRAS, and TP53.

What is Parasitology?

The study of organisms that live at the expense of a host.

What are the two types of Parasitism?

Obligate (must have a host) and Facultative (can live independently or as a parasite).

What is the difference between a Definitive and an Intermediate Host?

Definitive hosts are where the parasite reaches sexual maturity; Intermediate hosts are required for larval/developmental stages.

What are the three main morphological groups of parasites?

Protozoa (unicellular), Helminths (multicellular worms), Ectoparasites (live on host surface).

What are the primary transmission routes for human parasites?

Ingestion (contaminated food/water), skin penetration, and vector-borne (insect bites).

What is the 'Ventral Sucking Disk' in Giardia?

A specialised attachment organ that allows the protozoan to "suction" onto the intestinal wall, leading to malabsorption and foul-smelling, fatty diarrhoea

What is the difference between the 'Infective Stage' and 'Diagnostic Stage'?

Infective stage is the form that enters the host; Diagnostic stage is the form found in laboratory samples.

Why is 'Eosinophilia' a critical diagnostic marker for Helminths?

Eosinophils are WBC which attack large, multicellular parasites, and a high eosinophil count suggests a parasitic infection.

What is the global impact of 'Neglected Tropical Diseases' (NTDs)?

They affect billions of people and cause roughly 100 million DALYs, often in the poorest regions.

What is Primary Amoebic Meningoencephalitis (PAM)?

rare, almost always fatal brain infection caused by Naegleria fowleri (the "brain-eating amoeba").

Entry: Via the nose from warm freshwater (>25°C).

Pathology: Migration through the olfactory nerve to the brain.

How is Naegleria fowleri diagnosed and treated?

Diagnosis: CSF microscopy or PCR; Treatment: Amphotericin B.

What are the key clinical features of Loa loa (African Eye Worm)?

: It causes Calabar swellings (localised itchy swellings) and visible migration of the adult worm across the conjunctiva (surface of the eye).

How do you diagnose and treat Loa loa?

Diagnosis: Daytime blood microscopy or PCR; Treatment: Diethylcarbamazine (DEC).

Describe the 'Human Stage' of a Soil-Transmitted Helminth (STH).

Larvae penetrate skin, migrate through lungs/heart, swallowed into gut, mature into adults.

Why is PCR often preferred over microscopy for parasitic diagnosis?

PCR is more sensitive and can detect parasite DNA at low organism levels.

What causes 'Miliary TB'?

Systemic spread of Mycobacterium tuberculosis via blood, appearing as tiny spots on X-ray.

Why are parasitic diseases increasing in non-endemic countries?

Increased global travel/migration and Climate Change allowing vectors to survive in colder regions.